Journal Article (Review Article) DKFZ-2026-01814

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Precision Medicine in Pancreatic Cancer: Targeting KRAS and Beyond.

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2026
Springer Verlag France S.A.R.L. Paris

Targeted oncology nn, nn () [10.1007/s11523-026-01236-x]
 GO

Abstract: For the past decades, chemotherapy constituted the therapeutic foundation in advanced or metastatic pancreatic cancer. Despite significant advances in the molecular understanding, translation into tangible patient benefit has remained modest. Until recently, mutant KRAS, the dominant oncogenic driver, was considered undruggable, and only a small subgroup of patients potentially benefited from targeted therapies. With the emergence of KRAS inhibitors, most patients with pancreatic cancer in theory qualify for targeted therapeutics. Final results from the RASolute 302 trial showed clinically meaningful activity of RAS inhibition in patients with metastatic pancreatic cancer and paved the way for approval. Ongoing preclinical and coclinical studies have documented both intrinsic and acquired mechanisms of resistance to KRAS inhibition. Given the cellular plasticity seen in pancreatic cancer, the identification and anticipation of resistance mechanisms will be critical to exploit emerging therapeutic vulnerabilities through novel combination strategies. In view of the increasing number of trials and the growing body of evidence for targeted therapies, pancreatic cancer is entering a transitional phase in which precision oncology strategies must be redefined beyond rare molecular subgroups. In this review, we will briefly revisit targeted therapeutic approaches in pancreatic cancer to then discuss the clinical implications of genomic and transcriptomic heterogeneity in KRAS-mutant and KRAS wild-type disease. We will outline how our expanding biological insights into pancreatic cancer could inform combination and sequential therapeutic approaches.

Classification:

Note: #DKTKZFB9# / epub

Contributing Institute(s):
  1. DKTK Koordinierungsstelle Essen/Düsseldorf (ED01)
  2. DKTK Koordinierungsstelle München (MU01)
Research Program(s):
  1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2026
Database coverage:
Medline ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; DEAL Springer ; DEAL Springer ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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 Record created 2026-07-21, last modified 2026-07-22



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